CN110650764A

CN110650764A - Aerosol delivery system and method

Info

Publication number: CN110650764A
Application number: CN201880033710.0A
Authority: CN
Inventors: 夏恩·波特; 路易丝·斯威尼; 罗南·麦克朗林; 吉姆·芬克; 艾丹·达菲; 克莱尔·里利斯; 康纳·达菲; 弗兰·基廷
Original assignee: Stanford Equipment Co Ltd
Current assignee: Stanford Equipment Co Ltd
Priority date: 2017-03-23
Filing date: 2018-03-23
Publication date: 2020-01-03
Anticipated expiration: 2038-03-23
Also published as: EP3600503B1; AU2018240522B2; EP4088768B1; EP4306157A3; CA3057404A1; EP3600503A1; EP4088768A1; JP2022187012A; JP2020511280A; CN110650764B; JP7463474B2; AU2018240522A1; ES2925780T3; WO2018172563A1; EP4306157A2

Abstract

An aerosol delivery system includes an aerosol generator that nebulizes fluid for delivery to a patient upon inhalation by the patient. The aerosol delivery system includes a pump coupled to the aerosol generator that pumps the fluid to the aerosol generator; and a respiration sensor that emits a signal when the patient breathes. A controller is coupled to the aerosol generator, the pump, and the breath sensor. In operation, the controller receives the signal from the breath sensor, controls a flow of fluid to the aerosol generator in response to the signal and controls the aerosol generator to begin nebulizing the fluid prior to inhalation by the patient.

Description

Aerosol delivery system and method

Cross Reference to Related Applications

This application claims priority to U.S. application No. 62/475,603 filed on 23/3/2017, the entire disclosure of which is incorporated herein by reference for all purposes. This application also relates to U.S. provisional application No. 62/475,618 filed on day 3, 23, 2017 and U.S. provisional application No. 62/475,635 filed on day 3, 23, 2017, both of which are incorporated herein by reference for all purposes.

Background

This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present invention, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present invention. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.

There are many types of respiratory diseases that may affect the ability of a patient to breathe normally. These diseases may range from the common cold to cystic fibrosis. Modern medicine treats these diseases in a variety of ways, including oral medication, inhalers, nebulizers, and the like. Nebulizers are devices that change a fluid (i.e., a drug) into an aerosol for delivery to a patient by breath. The patient may receive the aerosol through an oral, nasal and/or tracheotomy (i.e., an incision made surgically in the throat). However, nebulizers may not be effective in treating respiratory diseases if the droplets of the aerosol are large and/or the aerosol formation does not properly time-coordinate with the patient's respiratory cycle.

Disclosure of Invention

The present invention relates to various embodiments of aerosol delivery systems. In some embodiments, the aerosol delivery system includes an aerosol generator that nebulizes fluid for delivery to a patient upon inhalation by the patient. The aerosol delivery system includes a pump coupled to the aerosol generator that pumps fluid to the aerosol generator; and a respiration sensor that emits a signal when the patient breathes. A controller is coupled to the aerosol generator, the pump, and the respiration sensor. In operation, the controller receives a signal from the breath sensor, controls fluid flow to the aerosol generator in response to the signal, and controls the aerosol generator to begin nebulizing fluid prior to inhalation by the patient.

In some embodiments, the aerosol delivery system includes an aerosol generator that nebulizes fluid for delivery to a patient upon inhalation by the patient. The pump is coupled to the aerosol generator, the pump pumps fluid to the aerosol generator, and the flow sensor is configured to sense a change in fluid flow upon inhalation by a patient. A controller is coupled to the aerosol generator, the pump, and the flow sensor. In operation, the controller receives a signal from the flow sensor, controls fluid flow to the aerosol generator in response to the signal, and controls the aerosol generator to begin atomizing the fluid.

One aspect of the invention includes a method of providing an aerosolized fluid to a patient. The method includes detecting a breathing cycle with a breathing sensor and then predicting the onset of inhalation. After predicting the onset of inhalation, the method pre-loads the fluid onto the vibratable member with the pump. Subsequently, the vibratable member is vibrated with the piezoelectric actuator to atomize the fluid.

Drawings

The various features, aspects, and advantages of the present invention will become better understood when the following detailed description is read with reference to the accompanying drawings in which like characters represent like parts throughout the drawings, wherein:

FIG. 1 is a schematic view of one embodiment of an aerosol delivery system coupled to a respiratory system;

FIG. 2 is a schematic view of an embodiment of an aerosol delivery system coupled to a respiratory system;

FIG. 3 is a schematic view of an embodiment of an aerosol delivery system coupled to a respiratory system;

FIG. 4 is a schematic view of an embodiment of an aerosol delivery system coupled to a respiratory system;

FIG. 5 is a perspective view of a catheter connector with a fluid flow sensor;

FIG. 6 is a perspective view of an embodiment of an aerosol generator coupled to a conduit connector;

figure 7 is a cross-sectional view of an embodiment of an aerosol generator coupled to a nasal cannula;

FIG. 8 is a diagram showing when the aerosol delivery system nebulizes fluid in relation to when the patient is breathing;

figure 9 is a perspective view of one embodiment of an aerosol generator system;

figure 10 is an exploded perspective view of one embodiment of an aerosol generator system; and

fig. 11 is an exploded perspective view of an embodiment of a positive displacement pump.

Detailed Description

One or more specific embodiments of the present invention will be described below. These embodiments are merely examples of the present invention. Additionally, in an effort to provide a concise description of these exemplary embodiments, all features of an actual implementation may not be described in the specification. It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business-related constraints, which may vary from one implementation to another. Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.

The embodiments discussed below include an aerosol delivery system that is capable of predicting patient inhalation in order to time the generation and delivery of an inhalable aerosol medicament. For example, aerosol delivery systems may anticipate inhalation so that the drug may be aerosolized prior to inhalation. By aerosolizing the drug upon inhalation by the patient, the aerosol delivery system increases the amount of drug delivered to the patient per breath, enhances the efficacy of the drug, and/or delivers the drug to a larger area within the patient's lungs (e.g., deeper into the lungs). Aerosol delivery systems use one or more breath sensors to detect inhalation by a patient. These respiratory sensors can detect inhalation in all modes of ventilation, including mandatory, auxiliary, and spontaneous. For example, aerosol delivery systems may use a flow sensor as a breath sensor to detect patient inhalation. As will be explained below, the flow sensor is more effective than the pressure sensor in detecting the start and stop of inhalation.

Aerosol delivery systems may also increase delivery effectiveness with aerosol generators capable of producing a Fine Particle Fraction (FPF) of greater than 80%, where the droplets/particles have a Volume Median Diameter (VMD) of 1 micron or less. In other words, the aerosol generator is capable of generating a very fine aerosol that is readily suspended in and carried by a carrier fluid (e.g., air, O2, O2/air mixture, etc.). Finally, the aerosol delivery systems discussed below can be coupled to existing respiratory systems without the need to redesign or re-engineer those systems. This enables the aerosol delivery system to be used with existing ventilators, humidifiers, Continuous Positive Airway Pressure (CPAP) machines, and the like.

FIG. 1 is a schematic view of one embodiment of an aerosol delivery system 10 coupled to a respiratory system 12. In fig. 1, the respiratory system 12 includes a ventilator 14 capable of forcing air (e.g., air, O2, air/O2 mixture, etc.) into and out of a patient. As will be explained in detail below, the aerosol delivery system 10 can be connected to a variety of existing respiratory systems 12 to provide aerosolized fluids (e.g., medicaments) for patient treatment. That is, the aerosol delivery system 10 may be retrofitted to existing respiratory systems 12 (e.g., ventilators, humidifiers, Continuous Positive Airway Pressure (CPAP) machines, or combinations thereof) without having to redesign or reengineer the respiratory system 12 to work with the aerosol delivery system 10.

The aerosol delivery system 10 includes an aerosol generator 16 that can be coupled to various airflow devices, such as an endotracheal tube 18, a nasal cannula/mask, a tracheostomy tube, and the like. The aerosol generator 16 receives fluid from a fluid source 20 through a fluid delivery conduit 22. The fluid source 20 (e.g., container, vial) can contain a variety of substances including drugs, surfactants, combinations thereof, and the like. In operation, fluid from the fluid source 20 is pumped by the pump 24 through the fluid delivery conduit 22 to the aerosol generator 16, where the fluid is aerosolized prior to and/or upon inhalation by the patient in the aerosol generator 16. In some embodiments, the fluid delivery catheter 22 may be primed with fluid prior to treatment to ensure rapid delivery (e.g., preloading of the fluid in the aerosol generator 16). The pump 24 is controlled by a controller 26, and the controller 26 schedules the delivery and dosing of fluids.

The controller 26 includes one or more processors 28 that execute instructions stored on one or more memories 30 to drive the operation of the pump 24 and the aerosol generator 16. For example, the memory 30 may include instructions that indicate the amount of fluid to be pumped to the aerosol generator 16 in each dose for each actuation of the aerosol generator 16, how much fluid to be pumped over a particular period of time, and the like. The stored instructions may be based on the size of the patient, the age of the patient, the sex of the patient, the type of medication, the fluid additive, the amount of aerosol desired, and the like. The memory 30 also includes instructions for activating the aerosol generator 16. As shown, the controller 26 is connected to the aerosol generator 16 with a cable 32 (i.e., an electrical cable), however, in some embodiments, the controller 26 may be wirelessly connected to the aerosol generator 16. The cable 32 carries a signal that activates a piezoelectric (or other) actuator inside the aerosol generator 16. When the piezoelectric actuator operates, it vibrates the vibratable member, which then atomizes the fluid for delivery to the patient (i.e., by inhalation). Thus, the memory may include instructions for controlling when the piezoelectric actuator starts, stops, a frequency or frequencies of vibration, and the like.

The aerosol delivery system 10 enhances the therapeutic effect by timing the generation of the aerosol. For example, the aerosol delivery system 10 may begin aerosolizing the drug prior to inhalation by the patient. In this manner, the aerosol delivery system 10 utilizes increased airflow at the beginning of an inhalation. This increases drug delivery to the patient as the inhaled air carries the drug deeper into the patient's lungs. The aerosol delivery system 10 may also nebulize the drug upon detection of an inhalation (e.g., for spontaneous breathing).

The aerosol delivery system 10 uses one or more breath sensors 34 to coordinate the delivery of the medicament to determine when and for how long the patient inhales. The respiration sensors 34 may include a flow sensor 36 (e.g., an amperage sensor), a radar sensor 38 (e.g., a UWB radar sensor for measuring chest displacement), CO₂Sensors, high speed temperature sensors 40, acoustic sensors 40, impedance plethysmography sensors 40, respiratory sensing plethysmography sensors, pressure sensors, and the like. These respiration sensors 34 may communicate with the controller 26 via a wired connection and/or a wireless connection. In some embodiments, the aerosol delivery system 10 may use a combination of respiratory sensors 34 (e.g., 1, 2, 3, 4, 5) to provide redundancy and/or to the respiratory cycle of the patientMore accurate monitoring. For example, the aerosol delivery system 10 may use the flow sensor 36 in conjunction with the radar sensor 38 to monitor airflow and chest movement. In another embodiment, the aerosol delivery system 10 may monitor the respiratory cycle using the flow sensor 36, the radar sensor 38, and the plethysmographic sensor 40.

As shown, flow sensor 36 is coupled to gas delivery conduit 42 to sense changes in gas flow during inhalation (e.g., forced, assisted, or spontaneous breathing). In some embodiments, flow sensor 36 may also be coupled to gas return conduit 44 to detect the beginning and end of exhalation. And in other embodiments, the aerosol delivery system 10 may include a flow sensor 36 coupled to a gas delivery conduit 42 and a gas return conduit 44. When controller 26 receives data from flow sensor 36, controller 26 may monitor the breathing pattern to predict when the patient will breathe. The ability to predict when an inhalation will begin enables the aerosol delivery system 10 to prepare the aerosolized drug for subsequent inhalation. More specifically, the aerosol delivery system 10 can preload the fluid on a vibratable member in the aerosol generator 16 so that the fluid can be nebulized prior to inhalation. Since flow detection is not a hysteresis indicator, flow sensor 36 may quickly detect an unusual or spontaneous inhalation (e.g., less than 10 milliseconds from the beginning of the inhalation) for delivery of the aerosol.

Predicting inhalation by the patient (if the patient is forced to ventilate) may be initiated by tracking the patient's breathing pattern and/or ventilation cycle using one or more breathing and/or flow sensors 36. The controller 26 then uses the tracked data to predict when a subsequent inhalation will begin. This allows the controller 26 to instruct the pump 24 to deliver fluid from the fluid source 20 to the aerosol generator 16 prior to inhalation. The controller 26 may also signal the aerosol generator 16 to begin nebulizing fluid at an appropriate time, such as within a predetermined time period (e.g., +/-0.5 seconds) before and/or during a predicted inhalation. In this way, the patient is prepared for aerosol at the beginning of inhalation. Although the aerosol delivery system 10 is capable of predicting a breathing cycle to generate an aerosol for a patient, the aerosol delivery system 10 can also use the breath sensor 34 to identify spontaneous/irregular breaths that are not part of the normal pattern. Once spontaneous breathing is identified, the aerosol delivery system 10 may immediately pump fluid to the aerosol generator 16 for delivery to the patient.

When the patient is forced (e.g., with the ventilator 14) or receives assisted ventilation, the flow sensor 36 is able to detect changes in flow as the ventilator 14 alternates between forcing air into and drawing air out of the patient. The controller 26 monitors these changes in flow rate and then calculates when to begin aerosolizing the drug, as discussed above. In this manner, the aerosol delivery system 10 may be integrated into an existing respiratory system 12 without the need to program or connect the systems together. In other words, the aerosol delivery system 10 and the respiratory system 12 need not communicate with each other to coordinate/time the generation and delivery of nebulization to the patient.

It should be noted that the flow sensor 36 is more capable of detecting when the patient has begun inhalation than the pressure sensor. Because it takes time to generate pressure in the air circuit, the pressure sensor provides an indication of the lag or delay. Thus, the pressure sensor will detect inhalation after or near the end of a breath. The pressure sensor is also ineffective in determining when inhalation is complete because the pressure sensor requires a continuous inspiratory pause (i.e., a plateau pressure when the patient pauses between inhalation and exhalation). Furthermore, in the event of leaks in the air circuit and/or kinks in the tubing, the accuracy of the pressure sensor can be greatly reduced. Finally, systems using pressure sensors would require powerful adaptive control algorithms to operate in forced, assisted, and spontaneous breathing situations, since ventilator breathing produces positive pressure, while spontaneous breathing produces negative pressure in the air circuit. However, in some cases, pressure sensors may be used with the aerosol delivery system 10 when the timing requirements for aerosol generation and delivery are not high.

As explained above, the aerosol delivery system 10 can be connected to a variety of existing systems to provide aerosolized fluids (e.g., medicaments) for patient treatment without the need to redesign or reengineer those existing respiratory systems 12 (e.g., communications). In fig. 2, the aerosol delivery system 10 is connected to a respiratory system 12, which includes a ventilator 14 and a warmer 60. Some respiratory systems 12 may include a warmer to humidify the air prior to inhalation by the patient. As shown, the gas delivery conduit 42 couples the warmer 60 to the ventilator 14 and the patient. As the air passes through the warmer 60, it is humidified before entering the endotracheal tube 18. In other embodiments, the gas delivery conduit 42 may be coupled to a nasal cannula, tracheostomy tube, or the like. The aerosol delivery system 10 is also coupled to an endotracheal tube 18, wherein the endotracheal tube 18 nebulizes fluid that is subsequently delivered to the patient.

A fluid source 20 (e.g., container, vial) containing a drug, surfactant, etc. is included within the aerosol delivery system 10. The fluid source 20 is fluidly coupled to the aerosol generator 16 with a fluid delivery conduit 22. In operation, fluid in the fluid source 20 is pumped by the pump 24 through the fluid delivery conduit 22 to the aerosol generator 16, where the fluid is aerosolized prior to and/or upon inhalation by the patient in the aerosol generator 16. The pump 24 is controlled by a controller 26 that controls the delivery volume and timing to the aerosol generator 16.

The controller 26 coordinates the delivery of fluid to the aerosol generator 16 and subsequent nebulization of the fluid by communicating with the breath sensor 34. In fig. 2, the respiration sensor 34 is a flow sensor 36, but other respiration sensors 34 may be used alone or in combination with the flow sensor 36. As shown, multiple flow sensors 36 are coupled to the respiratory system 12, but in other embodiments, a single flow sensor 36 may be coupled to the respiratory system 12. For example, the flow sensor 36 may be coupled to a gas delivery conduit 42 and a gas return conduit 44. In some embodiments, a single flow sensor 36 may be coupled to the respiratory system 12 upstream of the humidifier 60. Placing the flow sensor 36 upstream of the humidifier 60 may extend the life of the flow sensor 36 (e.g., the current flow sensor 36) by preventing or reducing contact between the flow sensor 36 and moisture added by the humidifier 60, although some embodiments may also feature a flow sensor 36 positioned downstream of the humidifier 60. Some embodiments may include a first flow sensor 36 upstream of the humidifier 60 and another flow sensor 36 downstream of the humidifier 60. The inclusion of two or more flow sensors 36 may provide redundancy in detecting the start and stop of patient inhalation and/or forced air delivery from the ventilator 14. In yet another embodiment, the aerosol delivery system 10 may include one or more flow sensors 36 coupled to a gas delivery conduit 42; and one or more flow sensors 36 coupled to the gas return conduit 44. The inclusion of flow sensors 36 on gas delivery conduit 42 and gas return conduit 44 may provide redundant monitoring, as well as more detailed information about when the patient starts inhaling, stops inhaling, starts exhaling, and stops exhaling. By monitoring the breathing cycle, the controller 26 is able to increase the effectiveness of the medicament by timing the generation and delivery of the aerosol.

Fig. 3 is a schematic diagram of one embodiment of the aerosol delivery system 10 connected to a respiratory system 12 including a Continuous Positive Airway Pressure (CPAP) machine 80 (e.g., nCPAP). In operation, the CPAP machine 80 pumps air to the patient's throat to prevent the airway from collapsing. In fig. 3, a CPAP machine 80 is coupled to a nasal cannula 82 with a gas delivery conduit 42. The nasal cannula 82 then directs air into the patient through the nose. As shown, the aerosol delivery system 10 is coupled to a CPAP machine 80 with a flow sensor 36 on the gas delivery conduit 42 and to a nasal cannula 82 with the aerosol generator 16. In some embodiments, the aerosol delivery system 10 is coupled at or near the end of an existing respiratory system prior to or at the patient interface. In this manner, the aerosol delivery system 10 may be coupled to an existing CPAP machine 80 without the need to redesign or reengineer the CPAP machine 80.

As explained above, fluid is pumped from the fluid source 20 through the fluid delivery conduit 22 to the aerosol generator 16 with the pump 24. The aerosol generator 16 then uses a piezoelectric (or other) actuator inside the aerosol generator to atomize the flow prior to and/or upon patient inhalationAnd (3) a body. The pump 24 is controlled by a controller 26 that schedules fluid delivery and the amount delivered to the aerosol generator 16. The controller 26 coordinates delivery of fluid to the aerosol generator 16 and subsequent atomization of the fluid by communicating with the flow sensor 36. In some embodiments, the aerosol delivery system 10 may use another respiration sensor 34 and/or an additional flow sensor 36 to redundantly sense the patient's respiratory cycle. Additional respiration sensors 34 may include radar sensors 38 (e.g., UWB radar sensors for measuring chest displacement), CO₂Sensors, high speed temperature sensors 40, acoustic sensors 40, impedance plethysmography sensors 40, respiratory sensing plethysmography sensors, and the like. The inclusion of two or more breathing sensors 34 may provide redundancy in detecting the beginning and end of a patient's inhalation.

Fig. 4 is a schematic diagram of one embodiment of the aerosol delivery system 10 connected to the respiratory system 12 including a warmer 60. Humidifier 60 adds moisture, with or without heating, to increase the humidity of the gas inhaled by the patient, thereby avoiding drying of the patient's airway. As shown, humidifier 60 is coupled to endotracheal tube 18 with gas delivery conduit 42. In other embodiments, the gas delivery conduit 42 may couple the humidifier 60 to a nasal cannula, tracheostomy tube, or the like. The aerosol delivery system 10 is also coupled to an endotracheal tube 18, wherein the endotracheal tube 18 nebulizes fluid for delivery to a patient.

The aerosol delivery system 10 includes a fluid source 20 (e.g., container, vial) containing a drug, surfactant, etc. The fluid source 20 is fluidly connected to the aerosol generator 16 with a fluid delivery conduit 22. In operation, fluid in the fluid source 20 is pumped by the pump 24 through the fluid delivery conduit 22 to the aerosol generator 16, where the fluid is aerosolized prior to and/or upon inhalation by the patient in the aerosol generator 16. The pump 24 is controlled by a controller 26 that schedules delivery and quantity of fluid received by the aerosol generator 16. The controller 26 coordinates fluid delivery and subsequent fluid nebulization by communicating with the breath sensor 34. In fig. 4, the respiration sensor 34 is a flow sensor 36. However, the additional respiration sensor 34 may be used aloneWith or with flow sensors 36 (e.g. radar sensors 38, CO)₂Sensors, high speed temperature sensors 40, acoustic sensors 40, impedance plethysmography sensors 40, respiratory sensing plethysmography sensors, etc.). Monitoring the inhalation and/or exhalation of a patient facilitates efficient delivery of the medicament, which can reduce the amount of medicament used to treat the patient, as well as the effectiveness of aerosolized medicament.

FIG. 5 is a perspective view of a catheter connector 90 having a flow sensor 36. As explained above, the aerosol delivery system 10 may be retrofitted to existing respiratory systems 12, which include the addition of one or more breath sensors 34 to detect inhalation and/or exhalation by the patient. In some embodiments, the aerosol delivery system 10 includes one or more flow sensors 36 coupled to one or more conduits (e.g., gas delivery conduit 42, gas return conduit 44). As shown, the flow sensor 36 rests within a conduit connector 90 (e.g., housing), the conduit connector 90 defining a first end 92 having an inlet 94 and a second end 96 having an outlet 98. In some embodiments, the first end 92 may be coupled directly to an outlet of a ventilator, CPAP machine, humidifier, or the like, while the second end is coupled to a conduit (e.g., gas delivery conduit 42, gas return conduit 44). In another embodiment, the first end 92 and the second end 96 may be coupled to conduits (e.g., gas delivery conduit 42, gas return conduit 44). In this manner, the flow sensor 36 may be retrofitted to existing breathing systems 12 without having to redesign or re-engineer the breathing system 12.

Figure 6 is a perspective view of one embodiment of the aerosol generator 16 coupled to an endotracheal/tracheostomy tube connector 110. The connector 110 enables the aerosol generator 16 to be fluidly coupled between the gas delivery conduit 42 and an endotracheal or tracheostomy tube 18 (seen in fig. 1). In this position, the connector 110 places the aerosol generator 16 closer to the patient, which increases the percentage of aerosol delivered to the patient. As shown, the connector 110 includes a first end 112 having an inlet 114 that may be coupled to the gas delivery conduit 42 for medical treatment using a ventilator, CPAP machine, humidifier, or combination thereof. In some embodiments, the first end 112 may not be coupled to anything, but rather receives the atmosphere surrounding the patient. A second end 116 having an outlet 118 is coupled to the endotracheal tube or tracheostomy tube 18 with a press fit connection, snap fit connection, threaded connection, welding, glue, etc. to secure the aerosol generator 16 to the patient.

As shown, the aerosol generator 16 includes a housing 120. Within the housing 120, the aerosol generator 16 includes a vibratable member and a piezoelectric actuator. In operation, the controller 26 drives the pump 24 (seen in fig. 1-4) to force fluid through the fluid delivery conduit 22 and into the housing 120. As explained above, the fluid delivery conduit 22 may be perfused with a fluid to pre-load the fluid onto the vibratable member. As the fluid enters the housing 120, it spreads over some or all of the vibratable members. The controller 26 then transmits an electrical signal to the piezoelectric (or other) actuator, which then vibrates the vibratable member and the atomizing fluid. The atomized fluid then exits the housing 120 through the outlet 122 and into the tubular connector 110.

In some embodiments, the housing 120 may extend through an aperture 124 in the tubular connector 110 such that the atomized fluid exits at an outlet 122 that is closer to a central axis 126 of the tubular connector 110. This may cause the carrier fluid stream 128 to pass through the tube connector 110 to capture a greater portion of the aerosol for delivery to the patient. In some embodiments, the outlet 122 of the housing 120 may be flush with the bore 124 in the tubular connector 110 or surround the bore 124. The housing 120 may be welded, glued, snap-fit, threaded, press-fit, etc. to the tubular connector 110. In some embodiments, the aerosol generator housing 120 may form a fluid-tight seal with the tubular connector 110 using a gasket, weld, glue, or the like to prevent contaminants from being inhaled by the patient.

Figure 7 is a cross-sectional view of an embodiment of an aerosol generator coupled to a nasal mask or nasal cannula. The nasal cannula 150 includes a body 152 having a nasal prong 154 extending away from the body 152. The nasal cannula 150 may include first and

second inlets

156, 158 that feed the carrier fluid 128 to an aperture 160 in the nasal prongs 154. However, some embodiments may include

inlets

156 or 158 to feed the carrier fluid 128 to the prongs 154. Similar to the discussion above, the aerosol generator housing 120 may extend through the aperture 162 and into the nasal cannula 150 such that the aerosolized fluid exits at the outlet 122 closer to the central axis 164. This may facilitate the flow of aerosol to the patient when the aerosol enters closer to the center of the carrier fluid flow 128 flowing through the nasal cannula 150. In some embodiments, instead of extending into the nasal cannula 150, the outlet 122 of the housing 120 may be flush with the aperture 162 or surround the aperture 162.

The housing 120 of the aerosol generator 16 may be coupled to the nasal cannula 150 using welds, glue, etc., or may be coupled using a snap-fit connection, a threaded connection, a press-fit connection, etc. In some embodiments, the aerosol generator housing 120 may form a fluid-tight seal with the tubular connector 110 using a gasket 164, weld, glue, or the like to prevent contaminants from entering the fluid flow inhaled by the patient.

As explained above, the aerosol generator 16 includes the vibratable member 168 that vibrates and atomizes the fluid in response to the piezoelectric actuator 170. Vibratable member 168 may be a light-defined vibratable member as described in U.S. patent publication 2016/0130715, published 5/12/2016, the entire contents of which are incorporated herein by reference for all purposes. The vibratable member may be made of a polymer, a metal alloy, or the like. In operation, the vibratable member 168 is capable of producing a Fine Particle Fraction (FPF) of 99.6% or more, with the droplets/particles having a Volume Median Diameter (VMD) of 4 microns or less. In some embodiments, aerosol generator 16 using vibratable member 168 is capable of generating 80% or more FPF, where the droplets have a VMD of 1 micron or less. Aerosols with these characteristics are readily suspended in and carried by carrier fluids (e.g., air, O2, O2/air mixtures, etc.) for effective delivery to a patient (e.g., delivery of drugs deeper into the patient's lungs).

Fig. 8 is a graph 190 illustrating aerosol generation with respect to a respiratory cycle of a patient. As explained above, the aerosol delivery system 10 includes one or more breath sensors 34 that sense when the patient inhales and exhales. After tracking the patient's breathing pattern and/or ventilation cycle (if the patient is forced to ventilate), the controller 26 can predict when inhalation will begin. This information is then used to pump the fluid to the aerosol generator 16 (e.g., preload the fluid on the vibratable member 168), as well as to signal the aerosol generator 16 to begin nebulizing the fluid. In this way, the patient is prepared for aerosol at the beginning of inhalation. Although the aerosol delivery system 10 is capable of predicting a breathing cycle to generate an aerosol for a patient, the aerosol delivery system 10 can also use the breath sensor 34 to identify spontaneous/irregular breathing that is part of an abnormal pattern. Once spontaneous breathing is identified, the aerosol delivery system 10 may immediately pump fluid to the aerosol generator 16 for delivery to the patient.

In fig. 190, line 192 represents aerosol generation by the aerosol generator 16 and line 194 represents airflow during inhalation. Peak 196 represents the maximum airflow to the patient. As shown, aerosol generation begins at time period 198 prior to inhalation by the patient. For example, time period 198 may be 1-10%, 1-15%, 1-20%, 1-30%, etc., relative to time period 200 representing the duration of an inhalation (i.e., flow of gas to the patient). Aerosol generation may continue for a period of time 202 before stopping near the end of inhalation. For example, aerosol production may stop 1-20%, 1-15%, 1-20%, etc. before the end of inhalation, relative to the time period 200 representing the duration of inhalation. In this manner, the aerosol delivery system 10 reduces medication waste by ceasing the generation of aerosol that may not be effectively delivered to the patient. In some embodiments, aerosol generation may continue throughout the time period 200 representing inhalation. Aerosol generation periods 198 and 202 may also vary depending on the type of treatment (e.g., medication), patient (e.g., gender, size, age, etc.). For example, aerosol generation may start and stop at different times relative to time period 200 (e.g., start earlier, start later, end earlier, end later). In some embodiments, aerosol generation may start and stop multiple times during time period 200. In other embodiments, the aerosol generator 16 may generate more aerosol at the beginning and/or before inhalation begins and then gradually reduce the amount of aerosol generated. The aerosol generator 16 may also work in reverse to gradually increase aerosol generation during inhalation (e.g., as airflow to the patient increases). In other embodiments, the aerosol generator 16 may gradually increase and then gradually decrease aerosol generation during inhalation (e.g., gradually increase aerosol generation to the peak of the airflow 196 and then gradually decrease aerosol generation thereafter).

Fig. 9 is a perspective view of one embodiment of the aerosol delivery system 10. As shown, the fluid source 20 is a fluid reservoir 220 coupled to the controller 26. Fluid reservoir 220 is connected to pump 24 with a pump connection line 222, pump connection line 222 enabling fluid to be drawn from fluid source 20 when pump 24 is activated by controller 26. The fluid may be a drug, a surfactant, or a combination thereof. Pump 24 may be a positive displacement pump configured to discharge a controlled amount of fluid from fluid source 20. For example, the pump 24 may be a peristaltic pump, rotary pump, reciprocating pump, plunger pump, gear pump, screw pump, or the like. In some embodiments, pump 24 may be a non-positive displacement pump. For example, the non-positive displacement pump may be a gravity feed system, such as a drip (e.g., an intravenous therapy drip). To control the flow of fluid from the drip, the gravity feed system may include a valve. In some embodiments, the non-positive displacement pump may be a rotary vane driven pump, a piezoelectric driven pump. To increase the accuracy of fluid delivery of a non-positive displacement pump, the system may include a liquid flow sensor, a fluid pressure sensor, and/or a volume detection sensor (e.g., dry/wet sensor, capacitive level sensor, exhaust pressure sensor).

As explained above, the controller 26 includes one or more processors 28 that execute instructions stored on one or more memories 30 to control the operation of the pump 24 and the operation of the aerosol generator 16. The controller 26 may be housed within a controller housing 224. Coupled to the controller housing 224 is a display 226 and one or more buttons 228. For example, the controller 26 may include a power button 230 for powering the controller 26 on and off, buttons that provide access to and navigation through one or more menus, and the like. In some embodiments, the display 226 may be a touch screen for interacting with the aerosol delivery system 10. The housing 224 may also define a recess 232 that receives the pump 24 such that the pump 24 is aligned with the perimeter of the housing 224 or substantially aligned with the housing 224. This may increase the aesthetic appearance of controller 26 and reduce accidental removal of pump 24 from controller 26 through contact with adjacent objects.

Fig. 10 is an exploded perspective view of one embodiment of the aerosol delivery system 10. As shown, the controller housing 224 includes a projection 250, the projection 250 extending away from the sidewall 252. When the fluid container 220 is coupled to the controller housing 224, the protrusion portion 250 protects the fluid container 220 from accidental removal and from objects that a user may attempt to place on top of the fluid container 220. In addition to the projection 250, the controller 26 includes a shaft 254 extending from the sidewall 252. The shaft is coupled to a motor within the container 26. In operation, the controller 26 activates the motor, which then drives the pump 24 via the shaft 254. In some embodiments, the controller housing 224 includes a plurality of apertures in the sidewall 252 that facilitate coupling the pump 24 and the fluid container 220 to the controller housing 224.

In fig. 10, the fluid container 220 includes a fluid containing portion 258 containing the fluid source 20 and a pump reservoir portion 260. The pump reservoir portion 260 receives the pump 24 when the fluid container 220 is coupled to the controller housing 224. In some embodiments, pump 24 is coupled to fluid source 20 within pump reservoir portion 260 with pump connection line 222. In this manner, fluid reservoir 220 prevents or reduces accidental disconnection of pump connection line 222 from fluid source 20.

FIG. 11 is an exploded perspective view of one embodiment of pump 24. As explained above, pump 24 is a positive displacement pump that enables a measured release of fluid from fluid source 20. In fig. 11, the pump 24 is a peristaltic pump. Pump 24 includes a pump housing 280 and a cover 282 covering a disposable tube 284 and rollers 286. Roller 286 is coupled to plate 288 with bearings 290. Bearings 290 enable roller 286 to rotate as plate 288 rotates in response to movement of shaft 292. When assembled, disposable tube 284 is wrapped around roller 286 such that roller 286 can press disposable tube 284 against the inner surface of cover 282. As roller 286 rotates within cover 282, it receives measured amounts of fluid from fluid source 20 and then drives those measured amounts of fluid through disposable tube 284. In some embodiments, disposable tube 284 is coupled to pump connection line 222 at inlet 294 and to fluid delivery conduit 22 at outlet 296. In another embodiment, disposable tube 284 is pump connection line 222, which is coupled to fluid delivery conduit 22. In yet another embodiment, disposable tube 284 is fluid delivery conduit 22 that is coupled to pump connection line 222 or directly to fluid source 20.

As discussed above, embodiments of the present invention provide an aerosol delivery system that can be retrofitted onto existing respiratory systems, such as ventilators, CPAP machines, humidifiers, and/or other respiratory systems. For example, a user may couple a conduit connector, such as connector 110, between an existing artificial respiratory system and a delivery lumen (such as found in a nasal cannula, mask, mouthpiece, endotracheal tube, LMA or tracheostomy tube, and/or other patient interface device). As detailed above, the catheter connector may define an open interior and may include and/or be coupled with one or more respiration sensors, such as a flow sensor, radar sensor, CO₂One (or a combination) of a sensor, a high speed temperature sensor, an acoustic sensor, an impedance plethysmography sensor, a respiratory sensing plethysmography sensor, a pressure sensor, or the like, configured to emit a signal to detect a breathing pattern as the patient breathes. The connector may further include and/or be coupled with an aerosol generator having an output in fluid communication with the open interior of the conduit connector. The user may interface with the delivery lumen with the airway of the patient. The air may be delivered to the patient using a respiratory system, wherein the patient's respiratory cycle is detected using a respiratory sensor as discussed in more detail above. The breath sensor may communicate a signal associated with the detected breath cycle to a controller, which may use the data to predict the start of a subsequent inhalation. ControllerThe fluid may then be preloaded onto the vibratable member, such as by pumping the fluid onto the vibratable member. The vibratable member may then be vibrated with the piezoelectric actuator to nebulize the fluid and introduce the nebulized fluid into the airway of the patient via the open interior of the catheter connector and the delivery lumen. In some embodiments, the process may further include coupling the pump to a fluid source and an aerosol generator using one or more fluid lines.

While the invention may be susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and have been described in detail herein. However, it should be understood that the invention is not intended to be limited to the particular forms disclosed. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the following appended claims.

Claims

1. An aerosol delivery system, comprising:

an aerosol generator that nebulizes fluid for delivery to a patient upon inhalation by the patient;

a pump coupled to the aerosol generator, the pump for pumping the fluid to the aerosol generator;

a respiration sensor that emits a signal when the patient breathes; and

a controller coupled to the aerosol generator, the pump, and the breath sensor, wherein the controller receives the signal from the breath sensor, controls a flow of fluid to the aerosol generator in response to the signal, and further controls the aerosol generator to begin nebulizing the fluid prior to or during the inhalation cycle.

2. The system of claim 1, wherein the respiration sensor is a flow sensor.

3. The system of claim 1, wherein the respiration sensor comprises at least one of a radar sensor, a carbon dioxide sensor, a temperature sensor, an acoustic pattern sensor, an impedance plethysmography sensor, and a respiratory sensing plethysmography sensor.

4. The system of claim 1, wherein the pump is coupled to the aerosol generator with a line perfused with the fluid.

5. The system of claim 1, wherein the aerosol generator comprises a piezoelectric actuator that actuates a vibratable member that atomizes the fluid by expanding and contracting.

6. The system of claim 5, wherein the vibratable member is a photo-defined vibratable member capable of producing greater than 80% of a fine particle fraction having a diameter less than or equal to 4 microns.

7. The system of claim 1, wherein the controller comprises a processor coupled to the respiration sensor and configured to predict when the patient will inhale by monitoring a respiration cycle of the patient.

8. The system of claim 1, wherein the pump is a positive displacement pump.

9. The system of claim 1, wherein the pump is a non-positive displacement pump.

10. An aerosol delivery system, comprising:

a pump coupled to the aerosol generator, the pump pumping the fluid to the aerosol generator;

a flow sensor configured to sense a change in fluid flow upon inhalation by a patient; and

a controller coupled to the aerosol generator, the pump, and the flow sensor, wherein the controller receives the signal from the flow sensor, controls a flow of fluid to the aerosol generator in response to the signal, and further controls the aerosol generator to begin nebulizing the fluid.

11. The system of claim 10, wherein the pump is coupled to the aerosol generator with a line perfused with the fluid.

12. The system of claim 10, wherein the aerosol generator comprises a piezoelectric actuator that actuates a vibratable member that atomizes the fluid by radial expansion and contraction.

13. The system of claim 12, wherein the vibratable member is a photo-defined vibratable member capable of producing greater than 80% of a fine particle fraction having a diameter less than or equal to 4 microns.

14. The system of claim 10, comprising a processor coupled to the flow sensor and configured to predict when the patient will inhale by monitoring a breathing cycle of the patient.

15. The system of claim 10, wherein the pump is a peristaltic pump.

16. A method of providing nebulized fluid to a patient comprising:

detecting a breathing cycle with a breathing sensor;

predicting the onset of inhalation;

preloading a fluid onto the vibratable member with a pump; and

vibrating the vibratable member with a piezoelectric actuator to atomize the fluid.

17. The method of claim 16, wherein detecting the respiratory cycle comprises detecting a change in flow with a flow sensor.

18. The method of claim 16, wherein preloading the fluid onto the vibratable member begins at least 1% before inhalation as measured by a predicted duration of breathing.

19. The method of claim 18, comprising stopping fluid flow onto the vibratable member after inhalation begins.

20. The method of claim 19, wherein the piezoelectric actuator continues to vibrate and atomize the fluid after the fluid flow stops.